Since the early 1970's there has been a strong interest in synthesizing alkali metal trisubstituted borohydride reagents because of their unique reactivity and synthetic utility in organic chemistry. Lithium trisubstituted borohydrides reagents, for example, are used in organic synthesis primarily as regioselective and stereoselective borohydride reducing agents. Most preparations of lithium trisubstituted borohydrides have focused on the reaction of lithium hydride or lithium aluminum reagents and trialkyl boranes to produce the above mentioned compounds. The reaction formula below represents the reaction of lithium hydride and a trisubstituted borane. ##STR1##
Unfortunately, there has been little success in synthesizing sterically hindered lithium trisubstituted borohydride reagents from commercially available lithium hydride and corresponding sterically hindered trisubstituted boranes. Indeed, a number of investigators have noted that hindered and highly hindered trisubstituted boranes are essentially inert towards lithium hydride. See, for example, Brown, H. C. et al., J. of Organometallic Chem., 166, 27-280 (1979); Brown, H. C. et al., J. of Organometallic Chem., 188, 1-10 (1980); Brown, H. C., Tetrahedron, 37, 2359-2362 (1981); and Thompson, et al., J. Org. Chem., 44:26, 5004-5005 (1979).
It is believed that processed or commercially available lithium hydrides are not highly reactive in such reactions. Even with special washing and activating procedures, sterically hindered trisubstituted borohydrides (for example, lithium tri-sec-butylborohydride) cannot be produced in commercially viable yields from commercially available lithium hydrides. See, Hubbard, J. L., Tet. Let., 29, No. 26 3197-3200 (1988). In that regard, the yields from such reactions are less than 10% in 24 hours based upon the amount of the limiting reagent consumed in the reaction.
There are some indication that lithium hydride (LiH) formed in situ, may be more reactive toward sterically hindered substituted boranes than commercially available LiH. For example, it is known that n-butyl lithium slowly thermally decomposes by evolution of 1-butene and precipitation of LiH. J. Org. Chem, 30, 4138 (1965). The generation of LiH from n-BuLi is more efficient by hydrogenation of n-BuLi in the presence of tetramethylethylenediamine (TMEDA). J. Am. Chem. Soc., 60, 2336 (1938); J. Am. Chem. Soc., 88, 5668 (1966); and J. Am. Chem. Soc., 52, 4299 (1987). One literature report indicated that LiH produced by this method with one equivalent of TMEDA was of sufficient reactivity to react with tri-sec-butylborane to generate lithium tri-sec-butylborohydride. Andres, H., Synthesis and Applications of Isotopically Labeled Compounds, 40-45 (1991); and 83-90, (1994). The present inventors have discovered, however that TMEDA, even when used in catalytic amounts, imparts impurities in the lithium trialkylborohydride which are detrimental to intended usage.
It is very desirable, therefore, to develop commercially viable methods of producing sterically hindered lithium substituted borohydride reagents that do not suffer from the problems associated with current synthetic routes.